P53-Dependent acinar cell apoptosis triggers epithelial proliferation in duct-ligated murine pancreas

The mechanisms linking acinar cell apoptosis and ductal epithelial prolifer ation remain unknown. To determine the relationship between these events, p ancreatic duct ligation (PDL) was performed on p53(+/+) and p53(-/-) mice. In mice bearing a wild-type p53 allele, PDL resulted in upregulation of p53 protein in both acinar cells and proliferating duct-like epithelium. In co ntrast, upregulation of Bcl-2 occurred only in duct-like epithelium. Both p 21(WAF1/CIP1) and Bax were also upregulated in duct-ligated lobes. After PD L in p53(+/+) mice, acinar cells underwent widespread apoptosis, while duct -like epithelium underwent proliferative expansion. In the absence of p53, upregulation of p53 target genes and acinar cell apoptosis did not occur. T he absence of acinar cell apoptosis in p53(-/-) mice also eliminated the pr oliferative response to duct ligation. These data demonstrate that PDL-indu ced acinar cell apoptosis is a p53-dependent event and suggest a direct lin k between acinar cell apoptosis and proliferation of duct-like epithelium i n duct-ligated pancreas.